The HIV epidemic among injecting drug users (IDUs) in NYC is the oldest and largest in the world. The proposed research will monitor trends and new developments in the three major components of this epidemic: HIV risk behavior, HIV infection, and HIV immunosuppression. Important recent large- scale changes include: increased safer injection associated with syringe exchanges, increasing intranasal use of heroin and cocaine, a trend towards safer sexual behavior, increased immunosuppression, and new initiatives to provide better health care for IDUs. We will also assess possible causal relationships among trends over time, and generalizability of findings to other sites. This research builds on our current New York and World Health Organization multi-site studies. Specific aims include: (1) monitoring trends in HIV risk behavior, particularly in association with syringe exchanges; (2) assessing the potential impact of increased intranasal drug use on HIV transmission; (3) monitoring HIV seroprevalence and assessing methods to estimate HIV seroconversion from cross-sectional survey data; (4) monitoring trends in HIV-related immunosuppression and in needs for health care services; (5) continuing our role as the U.S. component for the WHO multi-city study of HIV risk, including comparative analyses with other WHO study cities, especially Bangkok. We will conduct serial cross-sectional surveys with 300 injecting drug users and 200 intranasal drug users per year at the Beth Israel detoxification program. This program serves a geographically and demographically diverse clientele (including a subpopulation of newer injectors) with high frequencies of drug use. These characteristics, along with 10 years of historical data, make it an excellent site for studying trends in the HIV IDU epidemic in NYC, especially among high-frequency injectors, a critical group for the epidemic. The surveys will include HIV risk behaviors, HIV status, CD4 cell counts, factors associated with different routes of drug administration, and receipt of health care. We will assess generalizability of findings from the detoxification subjects through "street surveys," a parallel study conducted at a research storefront, and several allied studies. The trends we will study among this population of high-frequency injectors are likely to have substantial impacts on the HIV IDU epidemic nationally. Improved methods of estimating seroincidence from seroprevalence data would also contribute greatly to improved allocation of HIV prevention resources, as proposed under CDC guidelines. Within the proposed research, we will also continue our leadership role in the WHO multi-city study, which provides comparative analyses of risk behavior in developed and developing countries, as well as comparison with our findings from New York.